Andropause

In contrast to women, men do not experience a sudden cessation of gonadal function comparable to menopause. However, there is a progressive reduction in male hypothalamic-pituitary-gonadal axis function. Testosterone levels decline through both central (pituitary) and peripheral (testicular) mechanisms and there is loss of the circadian rhythm of testosterone secretion. Overall, at least 25% of men over age 70 meet laboratory criteria for hypogonadism (testosterone deficiency). This has been termed andropause or PADAM (partial androgen deficiency of ageing men) or popularly ‘male menopause’. It is thought to be responsible for a variety of symptoms in ageing men, including reduced muscle and bone mass, fatigue and erectile dysfunction.³ However, its diagnosis and the subsequent use of testosterone therapy are still controversial.⁴

Numerous cross-sectional and longitudinal studies indicate that testosterone declines with age (1% per year from 40 years). There is an even greater decline in free or bioavailable (free + albumin bound) testosterone, partly because of the 1.2% per year increase in SHBG (sex hormone-binding globulin).⁵ Despite the large body of evidence that testifies to a decline in testosterone with age, it is by no means universal. Numerous studies have demonstrated that fit and healthy men in their 70 s could achieve testosterone levels within the range expected for young men, provided they took regular exercise, were non-smokers, were not overweight and in general good health.⁶

The ADAM (androgen deficiency of ageing men) questionnaire forms a validated test for screening for symptoms related to a low testosterone level. In addition, the questions are informative themselves in defining the changes in a man associated with declining testosterone. In particular, they highlight that testosterone very much functions as a coping hormone in men. The questions are:

A recent study found that questions 1 and 7 were the most diagnostic of low testosterone (especially if three other questions were positive).⁷

A number of epidemiological studies have identified key factors associated with PADAM. For example, obesity and metabolic syndrome have been linked to accelerated testosterone decline.⁸ Alcohol use and stress are also implicated.^9,10 In turn, low testosterone predicts an increased risk of Alzheimer’s disease,¹¹ cognitive decline,¹² insulin resistance and type 2 diabetes.¹³ Low testosterone is associated with increased mortality in men and a higher risk of cardiovascular disease.¹⁴

A key herb in the management of PADAM is Tribulus terrestris. This herb possibly acts on the central regulation of testosterone production, at the level of the pituitary and hypothalamus. Clinical and in vivo studies have demonstrated increased testosterone, libido and sexual activity (see Tribulus monograph). Withania somnifera also improved testosterone levels in infertile men and boosted DHEAS (dehydroepiandrosterone sulphate) levels in stressed patients (see Withania monograph). Another traditional male tonic that will certainly help the stress and insulin resistance aspects linked to PADAM is Panax ginseng (see monograph). Serenoa repens is traditionally regarded as a herb for atrophy of the sexual tissues in both men and women and can be included in formulations to address the peripheral (testicular) decline in testosterone output (see monograph).

Low male fertility

About 15% of all couples are sub-fertile and the man is responsible in 30% of these cases. In another 20% abnormalities are detected in both partners.¹⁵ Ejaculation volume may be reduced, sperm count may be low or sperm may be abnormal. The cause in the male is usually unknown, although prescribed or recreational drugs can be identified in some cases. Excessive exposure to heat, as from hot tubs, can decrease sperm production, as can tight underwear. A percentage of men with varicoceles are sub-fertile because of them. Varicoceles can be treated with vascular herbs such as horsechestnut, gotu kola, butcher’s broom and the circulatory herbs listed below.

Treatment should attend to all lifestyle factors, since sperm are a reflection of the overall health of the male. Any major health problems and weaknesses, such as poor immunity, effects of stress, anxiety and so on, should be specifically addressed. A healthy diet rich in fruit and vegetables and low in refined carbohydrate should be observed.

Specific herbal guidelines for low fertility in the male are:

Erectile dysfunction

Obviously the development of drugs such as sildenafil has revolutionised the medical management of erectile dysfunction (ED). These drugs act as inhibitors of phosphodiesterase-5 (PDE-5) and increase cyclic GMP (cGMP). Maximal erectile function results from the relaxation of the smooth muscle of the penile arterial vessels through the activation of neuronal nitric oxide synthase (NOS), together with relaxation of the smooth muscle around the sinusoids of the corpora cavernosa through release of endothelial NO. The smooth muscle relaxation brought about by NO is mediated by cGMP release, and PDE acts to break down this cGMP. However, in most men with ED, poor lifestyle choices and resulting endothelial dysfunction and vascular disease result in insufficient NO and cGMP functions for the PDE-5 inhibitors to achieve their full potential.

ED in an otherwise healthy man is in fact a warning sign of endothelial dysfunction and impending vascular disease. In terms of risk factors, obesity is strongly associated with ED and the disorder is three times more common in diabetic men. In fact, one study found 12% of men with ED had unrecognised diabetes. Insulin resistance and metabolic syndrome are also risk factors for ED. In another study in men without diabetes, ED was strongly correlated with waist:hip ratio and was significantly improved by weight loss and exercise (with improved endothelial NO production). Smoking doubles the risk of ED, but limited alcohol intake is not a problem. ED is commonly co-morbid with hypertension, low testosterone, diabetes, obesity and benign prostatic hyperplasia and lower urinary tract symptoms (LUTS).^16,17

Some studies have delved deeper into the link between insulin resistance and ED. For example, a strong association was established between metabolic syndrome, insulin resistance and the incidence of ED. A fasting blood glucose >6.1 mmol/L was found to be positively correlated to increasing severity of ED.¹⁸

A systematic review and meta-analysis identified seven randomised controlled trials of Korean red ginseng in the treatment of ED.¹⁹ Six of the trials compared the effect of ginseng against placebo, enabling a meta-analysis. This demonstrated a highly significant and clinical relevant effect of ginseng on ED (p<0.00001). However, the authors cautioned that the low methodological quality and small sample size precluded absolute conclusions. Doses used in the trials were relatively high at typically 2 to 3 g/day (see monograph).

Specific herbal guidelines for ED are as follows:

Benign prostatic hyperplasia

BPH is a progressive, benign growth of the prostate gland that gradually narrows the urethra.²⁰ The clamping effect eventually obstructs the flow of urine. As a result, the bladder fails to empty completely. Urine remaining in the bladder stagnates, leaving the patient vulnerable to infections, bladder stones and kidney damage. The poor bladder capacity can cause frequent urination especially at night. Associated with BPH is therefore a set of LUTS. However, there is not always an exact correlation between the size of the prostate and the degree of LUTS, suggesting that other urodynamic factors are also involved.

The exact cause of BPH is not known and there have been various theories proposed.²¹ The recent understanding downplays androgens, both testosterone and dihydrotestosterone; their role is said now to be permissive. A higher oestrogen/testosterone ratio could be a causative hormonal factor. Increased peripheral conversion of testosterone to oestradiol by aromatase could be at play here.²¹ Chronic inflammation is also a common finding and one theory has proposed that BPH is an immune-mediated inflammatory disease caused by either infection or autoimmunity (more likely the latter).²² There is a strong link between chronic prostatitis and BPH.²³ Another theory proposes that higher circulating insulin stimulates prostate growth, and hence links BPH to insulin resistance.^24,25

Indeed, multiple experimental, clinical and epidemiological studies have demonstrated the link between either hyperinsulinaemia, elevated fasting blood glucose or type 2 diabetes and prostate enlargement and LUTS.²⁴ An association with obesity has also been observed.²⁶ The sympathetic overactivity linked to obesity, metabolic syndrome and hypertension may specifically increase the risk of manifesting LUTS.^27,28 LUTS and metabolic syndrome have been shown to be co-morbid, as has LUTS and ED. Improving testosterone can help symptoms of LUTS²⁹ and inflammation may also play a role in LUTS (insulin resistance is a pro-inflammatory condition); elevated serum C-reactive protein (CRP) correlates well with severity of LUTS.³⁰

Increased levels of physical activity have been associated with a decreased risk of BPH and LUTS in several large studies.³¹ A low fat, low animal protein diet appears to be protective, as does alcohol consumption against BPH, but it might increase LUTS.³² High glycaemic load foods appear to contribute to risk,^31,33 whereas consumption of fruit and vegetables appears protective.³⁴ A recent review of 14 studies confirmed the beneficial effect of exercise and proposed that decreased sympathetic tone, lower insulin resistance and reduced oxidative damage to the prostate could be the mechanisms involved.³⁵

Herbal remedies have a long history in the management of BPH/LUTS. The early association of the symptoms of prostatic enlargement (urinary frequency, retention and diminished flow) with ageing in men led to the inevitable association of remedies that reduced these symptoms with rejuvenating male tonics and promoters of male potency. Given the eternal demand for such agents, it is not surprising that they feature in most traditions. In some it is difficult to distinguish the stimulant aphrodisiac from the prostatic remedy; whereas cola (kola nuts) and Pausinystalia yohimbe (yohimbe), used in male virility ceremonies in west Africa, are obvious stimulants (the former a high caffeine source once briefly combined with the cocaine-containing coca leaves in the stimulant tonic drink of that name), it is less easy to distinguish the modest euphoric effects of high doses of the central American plant Turnera diffusa (damiana) from its reputation in aiding at least some of the problems of older men. Panax ginseng (Korean ginseng) was used particularly for elderly men in traditional Asian culture and is still favoured for prostatic enlargement symptoms – it has potential hormonal activity as a rationale. The most notable remedy from the southern USA is Serenoa repens (saw palmetto), initially used as a male tonic (as noted previously) but with increasing evidence of benefits in BPH. However, the consensus view appears to be shifting against its efficacy. Positive 1998 and 2002 Cochrane reviews³⁶ have been supplanted by a negative 2009 revision, which suggested that in a total of 26 studies there was no benefit above placebo.³⁷ (See the monograph for a discussion of these issues.) Saw palmetto is widely prescribed by urologists in Germany for early symptoms of benign prostatic hyperplasia, along with Urtica dioica (nettle root) and Curcurbita pepo (pumpkin seed).³⁸ There is consistent evidence for benefit in the case of Urtica in double blind, controlled studies (see monograph).³⁹ In the case of pumpkin seed, evidence is disappointing: one large multi-centre, placebo-controlled, double blind study on 542 early stage BPH patients looked at the effect of 500 mg standardised pumpkin seed extract or placebo twice daily for 12 months and found no difference in the two groups on subjective and laboratory measures.⁴⁰ The African remedy Pygeum africanum has been beneficial in clinical trials and is popular in France. However, it has been classified as an endangered species, with bleak prospects for its sustainability.⁴¹Crataeva nurvala improves bladder tone and decreases bladder emptying and is a useful symptomatic treatment for urinary obstruction, including that linked to prostatic enlargement (see the Urinary system in this chapter).

Specific herbal guidelines for BPH/LUTS are:

Chronic prostatitis

Prostatitis literally means inflammation of the prostate gland. It can be caused by a bacterial infection, in which case it is usually acute and short-lived. More common, however, is chronic prostatitis (also known as chronic prostatitis/chronic pelvic pain syndrome, CP/CPPS), for which the cause is basically unknown (bacteria are rarely involved). This painful and debilitating disorder can affect up to 15% of men at some stage in their lives and between 2% and 10% of adult men suffer from prostatitis at any given time.⁴² There is evidence suggesting that CP may be associated with an increased risk of prostate cancer (PC) as well as enlargement of the prostate (BPH).⁴²

The main symptoms of CP/CPPS are, as the name implies, chronic genitourinary pain or discomfort, with or without difficulties on urination. There is no known effective conventional treatment. Doctors often prescribe antibiotics, but they are rarely effective. Even if bacteria are involved (and they are mostly not), the prostate gland is notoriously difficult for antibiotics to gain effective access.

The exact cause of CP is unknown, but many relevant factors have been identified that probably all contribute to the problem. Feedback from patients is that prolonged sitting or riding a pushbike can make the condition worse, which suggests that poor circulation to the prostate is a probable factor. Many also complain that their pain flares up when they drink alcohol, so if this is the case it should be avoided.

From the published research, chronic inflammation possibly due to an autoimmune reaction is identified as an important factor. Men with CP have signs of significant inflammation in biopsy tissue taken from their prostates, with T cells apparently driving this reaction.⁴³ Another factor is stress. A study in Finland found that psychological stress is common in men with CP/CPPS.⁴⁴

One of the key herbs for CP/CPPS is saw palmetto, because of the thinking that it improves the overall health of the prostate gland. One clinical trial found a liposterolic extract of saw palmetto did not improve CP/CPPS,⁴⁵ but it can work well in combination, especially as the galenical. Another key herb is Echinacea, indicated to balance the immune system and also to help the body resolve any low level bacterial presence that might be driving the autoimmune response (also a case for urinary antiseptics such as buchu). Other relevant herbs include nettle root (which is again another herb to support the prostate), cramp bark and chamomile for pain and spasm. The Ayurvedic herb Crataeva is useful where bladder symptoms are also involved, since it is the best herb to support bladder function. Sometimes other immune herbs such as the mushrooms Ganoderma and shiitake can be valuable in stubborn cases.

In addition, herbs for chronic immune weakness such as Astragalus and tonic and adaptogenic herbs should be considered, as should mucous membrane tonic and anticatarrhal herbs such as golden seal and ribwort. Anti-inflammatory herbs may be appropriate, such as Bupleurum, Rehmannia and even Boswellia.

Prostate cancer

Older men are at increased risk of prostate cancer (PC), especially those with a family history and/or with a higher prostate specific antigen (PSA) level.⁴⁶ Autopsy results reveal that a man’s percentage risk of harbouring PC is about the same as his age in years. African Americans have a much higher risk. The risk is low in Asia, but when Japanese men move to the US their risk increases.⁴⁷ Infection and inflammation (prostatitis) also appear to be causative factors. Many men with PC also have prostatitis on biopsy and regular use of anti-inflammatory drugs lowers risk of developing PC. The role of androgens is unclear and controversial; 5alpha-reductase inhibitors may prevent the condition, but their value in studies might result from improved screening (more reliable PSA and biopsies).⁴⁸

PSA is a protease enzyme produced by the prostate to keep the semen liquid. The use of serum PSA to screen for prostate cancer is highly controversial. Some medical experts have likened it to ‘tossing a coin’. Around 75% of men with an elevated PSA reading do not have active PC and around 20% of men with PC will have a normal PSA. This is largely because elevated PSA is also associated with prostatitis and BPH.^46,49

A high-grade prostatic intraepithelial neoplasia (HGPIN or just PIN) may be found on biopsy. This is a pre-cancerous state, like carcinoma in situ, that can regress or progress.^50,51

The phenomenon of ‘watchful waiting’ (active surveillance) for men with intermediate PSA and/or Gleason score (GS) readings provides an opportunity for herbal management of men with low-grade PC. This is also the case for the pre-cancerous state HGPIN.

Key aspects of a plausible phytotherapeutic strategy are as follows:

In terms of downregulating inflammatory pathways in PC, herbs that can reduce NF-kappaB transcription should be emphasised.⁵³ A complex protocol mainly involving an anti-inflammatory herbal formula (rosemary, turmeric, ginger, holy basil, green tea, Polygonum, Coptis, barberry, oregano and Baical skullcap) was evaluated over 18 months in 23 men with HGPIN in an open label trial. The mean starting PSA was 6.13±3.56 ng/mL and by the end of the trial 48% of the men demonstrated a 25% to 50% reduction. Of the 15 participants who had the 18-month biopsy, 60% had reverted to benign, 27% still had HGPIN and 13% progressed to PC (GS 6). Serum CRP and NF-kappaB (in prostate tissue) were significantly reduced.⁵⁴

Baical skullcap flavonoids are being actively researched for antitumour properties, including PC models. Attenuation of NF-kappaB activity is a large part of this activity.⁵⁵ Curcumin has demonstrated apoptosis and a radiosensitising effect in prostate cancer cell lines (see also monograph).^56,57 Boswellia is anti-inflammatory and a boswellic acid (AKBA) induced apoptosis in PC cell lines and at 10 mg/kg suppressed PC tumour growth in mice and inhibited angiogenesis.^58,59 Red wine, but not alcohol, has been linked to a significantly lower risk of PC.⁶⁰ Resveratrol and OPCs are anti-inflammatory components found in wine. Grape seed extract inhibited advanced human prostate tumour growth and angiogenesis in mice at 100 mg/kg/day.⁶¹ Resveratrol at about 12.5 mg/kg suppressed PC growth in rats⁶² and inhibited NF-kappaB-regulated gene expression in PC cells.⁶³ In vitro and in vivo studies suggest that a key tumour-inhibiting mechanism for cat’s claw is suppression of NF-kappaB. Cat’s claw has also demonstrated clinical anti-inflammatory activity in a trial in rheumatoid arthritis patients.⁶⁴ Feverfew also has profound effects on NF-kappaB, but there are problems with bioavailability and hence an effective dose (see monograph).

In terms of phyto-oestrogens, there is promising research on linseed and isoflavones. Linseeds (30 g/day) for an average of 30 days prior to surgery significantly reduced cellular proliferation rates in a controlled trial involving 161 men with PC.⁶⁵ There were no changes in testosterone or PSA. Metabolites of the linseed lignans (such as enterolactone) inhibit PC cell growth in vitro.⁶⁶

There is good evidence from a recent meta-analysis of 14 epidemiological studies that soya foods will lower the risk of PC by around 26%.⁶⁷ Non-fermented sources of soya such as tofu or soya milk showed a higher degree of protection than fermented soya products such as miso. There is also good evidence that soy isoflavone supplementation can help patients with PC. Yet extraordinarily in 2007 the Cancer Council NSW, Australia, issued a press release warning patients with PC not to take soya foods ‘because they can accelerate the growth of tumours’.⁶⁸ Clinical studies with soya in healthy men have found favourable alterations in sex hormone levels and metabolism.^69,70 Prostatic fluid concentrations of isoflavones in soya consumers are sufficient to inhibit PC cell growth in vitro⁷¹ and isoflavones have been detected in prostate tissue after supplementation.⁷² In fact, prostatic levels exceeded serum levels.⁷³ Healthy men receiving 100 mg/day of soya isoflavones were protected from TNF-alpha-induced NF-kappaB activation (assessed in lymphocytes).⁷⁴ Four clinical studies have shown reductions in PSA or PSA velocity or other favourable effects in men with various stages of PC after intake of soya isoflavones or soya drinks. Typical isoflavone doses were 100 to 200 mg/day.^75–78 In a controlled trial 50 g/day of soya grits significantly reduced PSA and increased free PSA compared with a control wheat diet in men with PC scheduled for a radical prostatectomy.⁷⁹ Isoflavone intake is best increased via both diet and supplements.⁸⁰

The effect of an isoflavonoid-rich extract of red clover (60 mg/day isoflavones) on 20 men with elevated PSA levels (mean 10.16 ng/mL) but negative prostate biopsy was investigated over 1 year in an uncontrolled study. Mean PSA fell to 7.15 ng/mL (p<0.019).⁸¹ Randomised controlled trials are needed in biopsy-positive men.

In terms of immune regulation, investigations of medicinal mushrooms have mainly been undertaken. Activated hemicellulose compound is an extract of shiitake mushroom mycelia. It acts by enhancing cellular immune responses.^82,83 Modest benefits were observed in patients with advanced PC⁸³ and a dramatic remission was published for a patient with metastatic castration-resistant PC (GS 9).⁸⁴ Similar modest trial results were seen for a soya product combined with Ganoderma mycelia polysaccharides (5 g daily of the mushroom extract and also delivering around 900 mg/day isoflavones) in patients with PC.⁸⁵ However, another dramatic remission was published of a patient with confirmed PC (GS 6) who received a low dose of the product for 6 weeks.⁸⁶ PSA fell from 19.7 to 4.2 and no PC was found after prostatectomy. Cases such as these are a clear validation of applying the living with cancer principles in early stage cancers (see Chapter 8).

Green tea could prove to be a key herb in PC cell regulation, but promising results with silymarin from St Mary’s thistle are hampered by its poor access to the prostate. Preclinical (in vivo and in vitro) studies suggest that green tea and epigallocatechin gallate possess multi-targeted activity in PC.^87,88 Induction of apoptosis and reduction in NF-kappaB activity appear to be important in vitro mechanisms. Tea polyphenols were present in human and mouse prostate tissue after green tea consumption.⁸⁹

Early clinical studies with green tea were not promising, but both trials were in advanced, hormone-refractory PC patients.^90,91 A subsequent double blind, placebo-controlled study of 60 men with HGPIN over 1 year found that 60 mg/day of green tea catechins reduced LUTS and reduced the incidence of PC development (one case with green tea versus nine in placebo).⁹² A follow-up study of around half the men 2 years later (after no further treatment) found two more PC cases in the placebo group and one in the green tea group, establishing that the benefits were maintained.⁹³ Twenty-six men with positive biopsies took 1.3 g/day green tea catechins until surgery.⁹⁴ PSA was decreased, as were growth factors in prostatic tissue.

Silymarin has demonstrated multiple mechanisms of activity against PC in vitro and in vivo.^95,96 Silymarin also synergises with chemotherapeutic drugs in vitro.⁹⁷ One mechanism involves inhibition of multi-drug resistance pumps. However, after oral dosing of high amounts in men only very low levels were found in prostatic tissue.⁹⁸

The use of the PSA biomarker has provided for some interesting studies in prostate cancer. An uncontrolled study of pomegranate juice (8 oz daily containing 570 mg of polyphenolics) in men with rising PSA after surgery or radiotherapy was conducted in 48 patients with PSA 0.2 to <5.0 ng/mL and GS≤7. Mean PSA doubling time significantly increased from 15 months at baseline to 54 months post-treatment (p<0.001).⁹⁹

The research team of Dr Dean Ornish in the US has looked at the impact of diet in PC patients under watchful waiting. In the first study, a very low-fat vegan diet (12% dietary fat) plus supplements (soya, vitamin E, fish oil, selenium and vitamin C), exercise and stress management was compared to controls. PSA declined 4% over 12 months versus a 6% rise in the control arm. At follow-up 2 years later, 13 men in the control group had progressed to PC treatment versus just two in the intervention group. A second study with similar intervention examined prostate biopsies after 3 months. Gene expression changes in tissue consistent with lower tumourigenesis were observed. A low glycaemic index, moderate fat diet in four men for 6 weeks found favourable gene expression changes after radical prostatectomy compared with controls.^100,101

Hormone resistance

Declining endocrine function is one key manifestation of ageing. However, it appears to have been exacerbated in modern times by the phenomenon of functional hormone resistance, with insulin resistance being the least controversial, significant and most prevalent example.

Functional hormone resistance occurs when the endocrine gland produces adequate amounts of a given hormone, but the target cells are unable to utilise that hormone properly. The consequences are that either the effect of this hormone is reduced, or the body responds by producing more of the hormone to compensate. Both outcomes can lead to chronic health problems.

Insulin resistance is a curse of modern lifestyle that can lead to metabolic syndrome and type 2 diabetes. It has also been linked to a wide variety of other diseases such as breast and prostate cancer, PCOS (polycystic ovary syndrome), Alzheimer’s disease, gout and NASH (non-alcoholic steatorrhoeic hepatitis). Abdominal or central obesity (visceral adiposity) is probably the most significant issue in metabolic syndrome^1,2 and underlies the key metabolic change, which is insulin resistance.¹ ‘Insulin resistance syndrome’ is in fact an alternative name preferred by some scientists.

Many patients show clinical evidence of low thyroid function (especially low body temperature) but have normal laboratory tests for TSH (thyroid stimulating hormone), T3 and T4. It has been recently and controversially proposed that this phenomenon is due to thyroid hormone resistance (THR), similar to insulin resistance.³ This is not to be confused with subclinical hypothyroidism, which is medically defined as normal T3 and T4 with mildly elevated TSH (less than 10.0 MIU/L, normal range typically given as 0.3 to 5.5),⁴ although the two issues could occur together.

Subclinical hypothyroidism is usually associated with antithyroid antibodies but THR is not.⁴ Attributed causes of THR include mitochondrial dysfunction and environmental toxins including heavy metals, dioxins and pesticides acting as endocrine disrupters.³ Adrenal and thyroid function are connected, and elevated cortisol can interfere with thyroid function and possibly also lead to THR.⁵ It has also been proposed that chronic infection, chronic inflammation and hypercoagulation can cause THR.⁶

The most reliable method of diagnosis of THR is the symptom picture coupled with a positive Barnes Basal Temperature test. Temperatures below 36.6°C indicate hypothyroid function and possible THR if thyroid hormone tests are normal. A favourable response to thyroid treatment (phytotherapeutic or medical) confirms the diagnosis. Signs to look for include puffy face and lips, thinning hair and outer eyebrows, swollen skin, lack of alertness, cold extremities, weight gain and tendency to chronic infections. However, low thyroid function is the ‘great imitator’ that can mimic a vast number of medical conditions.

Functional cortisol resistance is probably even more controversial. The best example of chronic hyperactivation of the stress system (both the HPA axis and the noradrenergic system), probably due to a functional cortisol resistance, is melancholic depression.⁷ Hypersecretion of CRH from the hypothalamus has been shown in depression, with associated increases in ACTH and plasma cortisol. This hypersecretion of CRH is thought to be due to an impaired sensitivity of glucocorticoid receptors in the cerebral cortex, hypothalamus and pituitary, which impedes the normal negative feedback effect of cortisol. The higher amount of cortisol in melancholic depression has damaging effects leading to osteoporosis, metabolic syndrome, chronic infections and cancers.⁷ When not treated, these patients have a reduced life expectancy of 15 to 20 years, after excluding suicide. Other conditions possibly associated with functional cortisol resistance include anorexia nervosa, obsessive compulsive disorder, metabolic syndrome, chronic alcoholism and overtraining syndrome. In contrast, for fibromyalgia syndrome the resistance is probably to ACTH, rather than cortisol, due to poorly functioning adrenal glands.

The antidepressant activity of Rhodiola rosea is interesting in this context. Stress-activated protein kinase (SAPK, also known as JNK) inhibits the sensitivity of glucocorticoid receptors to cortisol. In an experimental model, both Rhodiola extract and salidroside decreased the release of SAPK/JNK and cortisone in response to stress. Hence the authors postulated that Rhodiola inhibits the stress-induced activation of SAPK/JNK in depressed patients and thereby restores the impaired sensitivity of glucocorticoid receptors to cortisol. Rhodiola also lowered awakening cortisol levels in patients with chronic stress and fatigue.⁸

The three key hormones discussed above exhibit functional relationships with each other. For example, exercise and weight loss-induced improvements in insulin resistance were blunted by poor thyroid status (subclinical hypothyroidism).⁹ The relationship between excess cortisol and insulin resistance or impaired thyroid function has already been discussed.

As touched on above, modern exposure to endocrine disrupters could play a significant role in endocrine disorders, including functional hormone resistance, metabolic syndrome, type 2 diabetes and hypothyroidism. One particularly relevant class of potent endocrine disruptors comprises the persistent organic pollutants (POPs).

These are mainly the organochlorines, which largely comprise the PCBs and DDT and metabolites. They have been banned from use in Western countries for several decades, but are incredibly stable in the environment and accumulate in fat tissue. Consumption of animal products means humans are particularly prone to POP accumulation. Some examples of their potential chronic effects on the body follow.

Serum levels of PCBs correlate with blood pressure, which is independent of BMI or age.¹⁰ In utero exposure to PCBs in concentrations slightly higher than average impacts on intellectual function.¹¹ PCB exposure from a waste incinerator was found to adversely impact thyroid function in children.¹² POPs including PCBs have been linked to increased incidences of oestrogen receptor-positive breast cancer¹³ and breast cancer in general.¹⁴

A major metabolite of DDT is DDE.¹⁵ The body’s DDE level is a risk factor for liver cancer, but associations with other cancers are controversial. Elevated DDE levels have been linked to CFS. DDT/DDE has been associated with female infertility, male infertility and miscarriages.

Gamma-glutamyltransferase (GGT) is the main predictor among serum liver enzymes for type 2 diabetes incidence.¹⁶ Relatively recently it has been linked to increased incidences of metabolic syndrome¹⁷ and insulin resistance.¹⁸ Even values at the high end of the normal range are predictive of a marked increase in risk. It has been shown that an increase in GGT predicts new onset of metabolic syndrome, incident (as opposed to silent) cardiovascular disease and death, suggesting that GGT is a marker of metabolic and cardiovascular risk.¹⁹

Various theories have been proposed, for example that GGT indicates the development of fatty liver disease¹⁶ or is a measure of inflammation and oxidative stress.²⁰ However, one compelling suggestion is that POPs are acting as endocrine disruptors, with GGT representing a measure of this exposure. After adjustment for all other known factors, including BMI and waist circumference, diabetes prevalence was strongly positively associated with POPs.²¹ In two studies, POPs (mainly as organochlorine pesticides) have been positively linked to insulin resistance²² and metabolic syndrome.²³

In humans BMI and fat mass are positively correlated with plasma POPs.²⁴ Lipolysis is associated with an increase in POP release, leading to a hyperconcentration of these pollutants in plasma and tissues during body weight and fat loss. This release of POPs during weight loss has been associated with decreased energy expenditure, such as resting metabolic rate. It accounts for around half of the adaptive drop in thermogenesis that occurs with weight loss. It is partly explained by a drop in T4 and T3, indicating significant endocrine disruption. POPs have even been described as environmental obesogens.²⁴

Such information regarding POPs highlights the need to support the body’s detoxification mechanisms where functional hormone resistance is evident. Enhancing phase I and especially phase II clearance by the liver is critical to reduce the burden of endocrine disruption, as is eating organic foods, especially animal products. Nutrients supporting the liver and providing the substrates of phase II clearance such as glutamine, glycine, taurine, cysteine, methionine and choline are important. Key herbs for boosting detoxification include Schisandra, rosemary (Rosmarinus), garlic (Allium sativum), green tea (Camellia), turmeric (Curcuma longa) and the Brassica species. Choleretic herbs also have a role since the phase II products will be largely excreted in the bile. During weight loss, supporting the hepatic metabolism of POPs becomes critical, as does additional thyroid support.

Arresting hormone decline

As mentioned above, the function of most endocrine glands declines with age, so it is relevant here to consider whether therapeutic plants can play a role in arresting endocrine ageing.

The industrialised world is facing a major challenge. The anticipated almost exponential increase in the number of older people will have dramatic and potentially disastrous consequences for public health, healthcare financing and delivery, informal caregiving and pension systems.²⁵ Take the US as a key example. In the US the proportion of the population aged 65 years or older is projected to increase from 12.4% in 2000 to 19.6% in 2030, being 71 million citizens. The number of people aged 80 years or older will more than double from 9.3 million to 19.5 million. By 2025 the proportion of Florida’s population aged 65 years or older is projected to be 26%. This demographic transition, which is due to the ageing of the baby boomers and increased life expectancy, represents a huge social challenge. About 80% of people aged greater than 65 years will have at least one chronic health condition, and 50% at least two. For example, about 10% of all adults aged 65 years or more will suffer from Alzheimer’s disease.²⁵

Should getting older be just about ‘nothing good happens’? Are we really meant to only become sicker and frailer as we age, with declining adrenal, thyroid and pancreatic function? The above quote from Woody Allen touches on a key issue here: that successful ageing is not just about living longer; it is about maintaining optimal mental, social and physical well-being and function.²⁶ In other words, healthspan is as important as lifespan, in fact even more so. Preserving endocrine function into old age is a key part of this.

The famous ageing researcher Leonard Hayflick once observed that ageing is ‘an increase in molecular disorder’.²⁷ One recently proposed theory that builds on this basic concept, and ties many ageing concepts together into one model, has been dubbed the ‘green theory’ of ageing. This model proposes that ageing is the result of damage to large key molecules, especially proteins, that has accumulated as a result of toxic metabolic byproducts (including damage caused by oxidation). A primary determinant of healthspan is therefore the efficiencies of either the protection against toxic products, the removal of these toxic products, including phase I/II detoxification by the liver, or the repair of this large molecule damage.^28,29 Protect, detoxify and repair is the catch-cry of preserving cellular health into old age.

The body has many pathways for detoxification, protection and repair:^30,31

According to the green theory, as long as these detoxification, protection and repair pathways are operating at their optimum efficiency, healthy ageing and preserved endocrine function should be a given. These themes sound remarkably like those in an old-fashioned naturopathy book. A key secret in achieving this goal is embedded in the concept of hormesis.

The term ‘hormesis’ was originally developed by toxicologists. In the recent context it conveys a simple message: what does not kill you makes you stronger. Medical and biological scientists now use the word hormesis to describe a key, fundamental concept of life: that moderate stress is not only healthy, it actually actively promotes optimum health. Hormesis therefore describes the beneficial adaptive response to moderate, healthy stress. It possibly represents the universal tonic and perhaps the one true fountain of youth.

Examples of hormesis in the research are many. For example, moderate levels of exercise promote excellent health, whereas excessive levels are debilitating and can lead to overtraining syndrome. There are countless examples from experimental models. For example, mild heat shock protected fruit fly larvae against a freezing shock that would normally kill them. Mild hypoxia stress can increase the lifespan of the roundworm (Caenorhabditis elegans) and can induce cross-tolerance to other types of stress.

The beneficial effects of mild to moderate stress (or hormetic effects) on ageing and longevity have been studied for several years, but especially in the last decade. In summary, mild to moderate stress has been found to increase longevity, delay behavioural ageing and increase resistance to other stresses in many animal models.^32–35

How can exposure to low levels of toxins or other stressors have beneficial effects? The answer lies in the defence molecules the body calls up in response to threats. Once rallied, these molecules not only deal with the immediate threat, but also increase resistance to other threats. They can even repair pre-existing damage, as per the green theory. Examples of these molecular defence agents include heat shock proteins (HSPs), sirtuin1, and the various beneficial growth factors and cell kinases. HSPs are produced when cells are exposed to high temperatures, toxins or inflammation. Their role is to protect (chaperone) other key proteins from damage by binding to them and shielding them from attack. Another ‘bodyguard’, sirtuin1 (or SIRT1), senses cellular stress and activates multiple genes that code for protective proteins such as antioxidants and cell-membrane stabilisers.³⁶

At this point it is worth mentioning the first class of herbs that can induce or mimic hormetic effects in the body: these are the adaptogens and they include ginseng (Panax ginseng), Rhodiola, Eleutherococcus and Withania. Recent research suggests that Echinacea root could be an adaptogen (see monograph). The basic theory of adaptogens was that they helped the body cope with stress by fine-tuning (and hence conserving) the stress response. They were also thought to support immune responses. However, current research has shed new light on how adaptogens might confer these benefits, and this is via hormesis.

It has recently been shown that the stress-protective effect of adaptogens is not the result of an inhibition of the stress response, but actually the result of the adaptation of the organism to the mild stress-mimicking effect of the adaptogen. In other words adaptogens mimic healthy stress in the body and turn on protective hormetic-response molecules, such as HSPs, thereby extending healthspan.^37,38

Another key antiageing concept that ties in well with the green theory and hormesis is the value of calorie restriction (CR). All ageing researchers universally acknowledge that dietary restriction or CR by 20% to 40% is proven to extend lifespan by up to 50%. No other known intervention has such a consistent and profound effect: experiments on single yeast cells up to primates have verified this outcome. But the key story here is not the extension of lifespan; it is the significant compression of morbidity (or extension of healthspan and normal endocrine function) that also takes place. At advanced ages CR animals are more youthful-looking, display inquisitive behaviour and are highly active, just like much younger animals. The exact way that CR works to extend youthfulness and lifespan is not fully understood, but several researchers have proposed that it is due to hormesis, with CR acting as a moderate healthy stressor.^39–41

A strong advocate of the hormesis hypothesis for CR is Dr David Sinclair, an Australian scientist working at Harvard on ageing research. He argues that the hormesis hypothesis links so many of the diverse observations about CR from experimental models. The pathways involved are a hardwired survival mechanism to enhance the chance of survival during stress and reduced food availability – a defensive response to a survival threat. Sinclair proposes that this very basic survival mechanism should be and is regulated by a few genes and their corresponding proteins. These genes have been identified as SIRT1 to 7. SIRT1 is particularly important. The sirtuin proteins are increased in CR and regulate a multitude of beneficial metabolic effects, as noted above.

Since phytochemicals can cause hormetic responses and may act as environmental signals to shift into survival mode ahead of an environmental decline, Sinclair’s team investigated whether simple phytochemicals might increase the SIRT1 protein. Resveratrol, found in grapes and several other foods and herbs, was identified to be the most active natural agent at activating SIRT1.⁴²Polygonum cuspidatum, the giant knotweed from Chinese traditional medicine, is a rich phytotherapeutic source of resveratrol. This plant is a common weed in many countries.

CR in practice can be difficult. The mental and physical stress of being hungry in conjunction with a modern life might provide more stress than is beneficial for a hormetic effect. Depression- and anxiety-like symptoms have been observed in CR rats. Diminished libido is a common side effect in humans and animals. CR might also reduce resistance to infection.^39,40

A more compelling strategy to practising actual CR is to find herbs and other supplements that can mimic its effects in the body, in the same way that adaptogens might directly mimic hormesis. The best example of how to do this to date is resveratrol (see above). In yeast cells, resveratrol was found to mimic CR by stimulating Sir2 (the yeast equivalent of SIRT1), and as a result increasing DNA stability and extending lifespan.⁴² Resveratrol significantly increased the survival of mice fed a high calorie diet and caused favourable physiological changes similar to CR.⁴³ While the intense focus has been on resveratrol, other phytochemicals have been shown to activate SIRT1 or the SIRT1 pathway in various in vitro models. For example components of silymarin from Silybum (St Mary’s or milk thistle) are active.^44,45

In addition to resveratrol, there are other ways to mimic CR effects in the body. Three key biochemical changes are observed in CR primate experiments: reductions in body temperature (by around 0.5°C), and plasma insulin, and a prevention of the decline in DHEAS. When men in the Baltimore Longitudinal Study on Ageing were divided into upper and lower halves for each of these values, there was a clear survival benefit observed.⁴⁶ The most marked survival benefit was observed for a higher level of DHEAS, followed by a lower level of insulin. A lower body temperature might reflect the benefits of slower metabolism, better oxidative control and reduced workload for the thyroid. Lower insulin probably results in lower AGEs and other favourable metabolic effects, and a higher DHEAS possibly reflects the sparing of the adrenal glands. On the insulin resistance front, metformin (a diabetes drug that promotes insulin sensitivity) prolonged lifespan in rodents and additionally seems to cause biochemical changes similar to CR.⁴⁷ Insulin resistance is known to contribute to the risk of developing many chronic diseases (see above and elsewhere in this chapter).

Hence, the beneficial consequences of CR can be simulated by improving insulin sensitivity (lowering insulin resistance) and better preserving DHEA. Perhaps not surprisingly, the adaptogens can help to improve DHEA levels. After oral administration of 6 g of Korean red ginseng for 30 days to postmenopausal women, DHEAS was increased by around 13%. Withania (Withania somnifera) significantly increased DHEAS by 30% in a placebo-controlled clinical trial (p<0.001).^48,49

Research has found that many herbs can improve insulin sensitivity. But two herbs are key in a healthy ageing context. A placebo-controlled clinical trial found that a St Mary’s thistle extract (delivering 600 mg/day of silymarin) for 4 months exerted a beneficial effect on glycaemic profile in relatively well-controlled patients with type 2 diabetes (on medication). There were also significant reductions in HbA_1c (13%), fasting blood glucose (15%), total cholesterol (12%), LDL-cholesterol (11%) and triglycerides (25%).⁵⁰ In well-controlled type 2 diabetic patients, ginseng caused no change in HbA_1c or fasting plasma glucose in a placebo-controlled clinical trial. However, fasting plasma insulin was significantly reduced by the ginseng (by 34%), whereas it increased in the placebo group (by 10%). In other words the ginseng lowered insulin resistance.⁵¹

In summary, the phytotherapeutic approach to healthy endocrine ageing should:

Four key herbs discussed above meet many of these targets, being Polygonum cuspidatum (with resveratrol), St Mary’s thistle (with silymarin), ginseng and Withania.

Adrenal depletion

Adrenal depletion can be defined as a reduced capacity to cope with stress. It usually arises from the chronic effects of continued stress brought about by the pace and demands of modern living. In a sense it represents a precursor state to chronic fatigue and fibromyalgia syndromes. Although not recognised as a medical condition, this syndrome is very common and often underlies why patients seek herbal treatment for fatigue. Typical signs and symptoms of adrenal depletion include constant fatigue and need for extra sleep, inability to cope with stress, irritability and anxiety, reduced libido, sighing and yawning, low back pain in the adrenal area, recurrent and often prolonged colds or influenza, sweet craving and reactive dysglycaemia, sensitive to cold and heat and low core temperature. Pigmentation in skin creases and loss of body hair may be evident, as can poor digestion and assimilation, postural hypotension (Raglan’s sign) and unstable pupillary reflex.⁷²

Treatment for adrenal depletion includes the following objectives:

Idiopathic reactive hypoglycaemia

Reactive hypoglycaemia (RH) is a postprandial hypoglycaemic state occurring 2 to 5 hours after food intake. While it can occur in association with diabetes, gastrointestinal dysfunction and hormone deficiency states, a large patient group is characterised as having idiopathic RH.⁷³ The definition of idiopathic RH is controversial. Patients with idiopathic RH are proposed to have a delayed discharge of insulin that occurs inappropriately with falling levels of plasma glucose. It might also result from an exaggerated insulin response or a high insulin sensitivity.⁷³ It has been suggested that RH can occur in lean young women with polycystic ovary syndrome (PCOS), where it could be predictive of future diabetes.⁷³ RH is generally more common in people with low body weight.⁷⁴

Postprandial RH is characterised by sympathetic and neuroglucopenic symptoms developing concurrently with a lower blood sugar.⁷⁴ These include anxiety, trembling, sweating, hunger, dizziness, poor concentration and headaches. Being postprandial, symptoms typically occur mid-to-late mornings and afternoons.

People with RH are probably more sensitive to a drop in blood sugar, possibly due to excessive caffeine intake, stress and/or poor cerebral blood flow.⁷⁵ Diet is an important issue. Generally there is excessive consumption of refined carbohydrates and a low protein intake (especially at breakfast). Adrenal depletion can mean that counter-regulatory mechanisms of blood sugar control are not adequate.

Basic dietary advice is as follows:

Herbal treatment includes the following objectives:

Metabolic syndrome

As noted above, metabolic syndrome is an insulin-resistant state and as such is a precursor to type 2 diabetes. It is characterised by a cluster of cardiovascular risk factors and was first proposed in 1988, although alluded to in earlier literature.⁷⁶ These include various combinations of abdominal obesity, glucose intolerance, hypertension and atherogenic dyslipidaemia. The dyslipidaemia includes elevated triglycerides, low HDL-cholesterol, elevated apolipoprotein B and small LDL particles.

There are three main definitions of metabolic syndrome.⁷⁷ The first was developed by the WHO in 1998 with hyperglycaemia and insulin resistance as a central feature, associated with two or more related metabolic abnormalities (hypertension, dyslipidaemia, abdominal obesity or micro-albuminuria). Up until this consensus definition, metabolic syndrome was not widely accepted as a medical entity and it is still controversial. The US National Cholesterol Education Program (NCEP) definition requires three or more of: abdominal obesity, elevated triglycerides (>1.7 mmol/L), low HDL-cholesterol (<1.0 mmol/L men, <1.3 women), hypertension (>130/85 mmHg) or elevated fasting glucose.⁷⁷ In 2005 the International Diabetes Federation (IDF) proposed a definition similar to the NCEP, but elevated abdominal obesity as a necessary requirement.

The prevalence of metabolic syndrome has reached alarming proportions.⁷⁷ Depending on the definition, the incidence in US adults aged 20 years or more is between 35% and 39%. For Australia the estimated prevalence is between 24% and 26%. Metabolic syndrome is more prevalent with increasing age, affecting about 50% of adults aged 60 years and over. It is also more common in men. Despite the current high incidence, the prevalence of metabolic syndrome is increasing. For the first time in decades, medical scientists are proposing that the average life expectancy might fall in industrialised countries.

The key aspects of management of metabolic syndrome are:

It is acknowledged by all consensus groups that metabolic syndrome is linked to lack of physical activity.⁷⁸ Physical activity not only assists weight loss, it also improves insulin sensitivity. The current recommendation of the US American Heart Association for metabolic syndrome is at least 60 minutes of continuous or intermittent aerobic activity a day. Resistance training is also recommended.

A 2007 study compared a low GL diet against a low fat diet in obese (BMI >30) young adults.⁷⁹ For those with insulin resistance, the low GL diet produced a greater decrease in weight (−5.8 versus −1.2 kg, p=0.004) and body fat percentage (−2.6% versus −0.9%, p=0.03) than the low fat diet at 18 months. There was no significant difference for these measures between diet groups for those with a normal insulin response. In the full cohort, HDL-cholesterol increased and triglycerides decreased more on the low GL diet, whereas LDL-cholesterol decreased more on the low fat diet.

Key herbs and their rationale in the management of metabolic syndrome are as follows:

Being a highly complex disorder, the treatment strategy for metabolic syndrome will vary depending on the specific issues for the patient. Lifestyle and dietary changes and a reduction in central adiposity must be set as the primary objectives in the initial stages of treatment. Herbs for the insulin resistance and to improve glycaemic control should also be a priority.

Be guided by the case: for example, if there is a fatty liver and high ferritin then Silybum is the herb of choice (as the silymarin concentrate). If there are sugar cravings and borderline diabetes, preference should be given to Gymnema. If there is hypertension then hawthorn could be included. Stress management and attention to the cardiovascular and other metabolic disturbances, as indicated by the case, can be prioritised as appropriate.

Type 2 diabetes

In a 2008 editorial of the Medical Journal of Australia, the growing epidemic of type 2 diabetes in Australia was described as a ‘juggernaut’.⁸⁰ In an older population (Blue Mountains Eye Study) the overall incidence was 9.3%, with impaired fasting glucose in another 15.8% of participants.⁸¹ A 2003 study found that the prevalence of type 2 diabetes has doubled in the past 20 years to represent >7% of Australian adults.⁸² The incidence is also rising rapidly in children and adolescents.⁸³ These findings would also be typical of most Western countries.

The primary aim in type 2 diabetes is to achieve better glycaemic control through herbs, nutritional supplements, diet and exercise. However, type 2 diabetes is a chronic progressive disease which attacks the eyes, kidneys, nerves and blood vessels. Hence therapies aimed to treat and prevent these complications may also be necessary.

In terms of the diabetic complications, three major metabolic issues appear to be involved.^84,85 These are glycosylation of proteins, disturbances of the polyol pathway and inflammation and oxidative stress.

Glycosylation of proteins is directly related to glucose levels in the blood. Later stages are represented by the formation of irreversible advanced glycation endproducts (AGEs). These are a direct product of glucose concentration, time and oxidant stress. AGEs are potentially pathogenic; they accelerate atherogenesis, enhance protein deposition and cross-linking, derange normal physiology and create oxidative damage and inflammation.⁸⁴

Not all tissues require insulin for glucose transport, for example nerves, the lens, kidneys, blood vessels and endothelium.⁸⁶ Hyperglycaemia leads to an increase in intracellular glucose in these tissues, which is subsequently metabolised by aldose reductase (AR) into sorbitol, a polyol, and eventually fructose. This causes cellular damage. Increased activity of the hexosamine pathway can also lead to disturbed cell function via increased fructose production.

Hyperglycaemia increases oxidative stress through several pathways, including the interaction of glycosylated proteins with receptors (RAGEs) as noted above.⁸⁵ A major mechanism appears to be the overproduction of the superoxide anion by the mitochondrial electron transport chain. Hyperglycaemia also promotes inflammation via increased cytokine induction.

Flavonoids and related compounds show strong inhibitory activity on aldose reductase (AR) in vitro. Licorice and baicalein from Baical skullcap (Scutellaria baicalensis) have shown significant AR inhibitory activity in an animal model and could prove to be useful in preventing some of the long-term complications of diabetes.⁸⁷ Treatment with silybin (231 mg/day for 4 weeks) in 14 type 2 patients resulted in significant reduction of red blood cell sorbitol levels (suggestive of AR inhibitory activity, see monograph).

A link between ferritin, iron stores and type 2 diabetes has been proposed.⁸⁸ Frequent blood donations improve insulin sensitivity and glycaemic control in normal people and diabetics. Iron stores may contribute to diabetic complications, and being a frequent blood donor appears to confer some protection against developing type 2 diabetes. A correlation between serum ferritin and diabetic retinopathy has been observed.⁸⁹ Silybum (St Mary’s thistle) as the concentrated extract has been shown to lower serum ferritin in a clinical study (see St Mary’s thistle monograph).

The glycaemic index is an assessment of the rate of glucose elevation in the bloodstream following the intake of a particular food. Any herb which delays gastric emptying will reduce the glycaemic index. These include mucilage herbs and other sticky fibre foods. Tannins (e.g. grape seed) also interfere with digestive processes, and saponins (e.g. Gymnema) can disrupt glucose transport (see also Chapter 2).

Key herbs to consider on the basis of the individual case in type 2 diabetes include:

Clinical and subclinical hypothyroidism

An underactive thyroid is a common condition that may often go undiagnosed. Because of the difficulty in detecting an underactive thyroid from symptoms, clinicians now rely heavily on laboratory tests. These thyroid function tests usually measure thyroid stimulating hormone (TSH, produced by the pituitary gland) and thyroid hormone output (T3 and T4). Also if it is suspected that a disease is causing the poor thyroid function, such as a disturbance of the immune system as in Hashimoto’s disease, then other tests such as antibody tests may be conducted.

If TSH is raised and T4 is low (that is, the stimulus to the thyroid is higher than normal, but its output is lower than normal), this is diagnostic of an underactive thyroid. Sometimes TSH is raised, but T4 is normal. This is termed sub-clinical hyperthyroidism. But how accurately do the blood tests reflect ideal thyroid function? Thyroid hormones regulate many key functions of the body and levels in the blood do not always reflect what is happening in the tissues.

This point was underlined by the case history of a 12-year-old boy who had many of the characteristic signs and symptoms of an underactive thyroid, such as increased body weight, lethargy, no appetite, puffy face, poor initiative and relatively slow pulse. Yet his thyroid function tests were normal. He had previously suffered from an overactive thyroid that had been treated with the standard drugs. Whether the drugs overcorrected, or whether his thyroid just naturally went underactive, could not be known for certain. But the important observation was that his tests were normal when his guardians were claiming he was a very different boy to when he was normal. See also p. 338 on THR.

It has been suggested that the diagnosis of hypothyroidism on the basis of thyroid function tests is flawed.⁹⁰ A better way to assess thyroid function is to measure basal metabolic rate (BMR), but this is seldom used. Some time ago Barnes suggested that many people have subtle thyroid dysfunction that the blood tests fail to detect, and controversially advocated the use of basal body temperature (BBT) to assess BMR.⁹¹ BBT is measured using a thermometer placed under the armpit on waking for 5 consecutive days. (For menstruating women measurement should start on day 2 or 3 of the cycle.) Readings less than 36.6°C (97.8°F) can indicate underactivity.

The key plant used to boost thyroid function is bladderwrack (Fucus vesiculosis). Bladderwrack is a shore-dwelling seaweed containing fluid-filled bladders that allow it to float as the tide comes in, hence its name. The part used is the whole seaweed plant, known as the thallus. The common understanding of this herb is often confused. It is not the same as kelp (although many people call it this). Kelp is a large, deep-sea seaweed harvested in significant quantities from ocean-going ships. In contrast, bladderwrack is collected by hand from inter-tidal regions. Although both kelp and bladderwrack, like all seaweeds, are rich sources of iodine, herbalists believe that bladderwrack additionally contains organic-bound iodine, which stimulates thyroid function in a way that simple iodine supplementation cannot.

Experiments as early as 1910 indicated that oral doses of bladderwrack had a stimulatory action on the thyroid gland.⁹² In a controlled clinical trial, overweight participants taking bladderwrack extract in addition to a controlled diet achieved a significantly greater average weight loss than those on the diet alone.⁹³

Caution does need to be exercised when taking bladderwrack, especially long term. Kelp and bladderwrack can cause overactive thyroid in the short term, and if taken in excess quantities over a long period can even induce a compensatory phenomenon that results in an underactive thyroid.^94,95 However, on the other hand, to be effective at stimulating thyroid function at least 3 to 4 g/day of bladderwrack is needed, or its equivalent in extract form.

Another herb with a mild stimulatory effect on the thyroid is the root of Withania somnifera.^96,97 Withania is widely regarded as a tonic (see monograph). Its stimulatory effect on thyroid output was shown in an in vivo model, especially on T4 output (which indicates a direct effect on the thyroid).^96,97 How it works is not known, but this herb favourably influences the function of several endocrine glands, as does another herb from India Coleus forskohlii. Coleus makes thyroid-hormone producing cells in the thyroid more sensitive to the effects of TSH (see p. 342).

If thyroid autoantibodies are above normal, then active thyroid destruction is occurring and these autoimmune manifestations should be taken into account during treatment (see Chapter 8). Issues pertaining to endocrine disruption should also be investigated (as discussed above) and antithyroid dietary components:⁹⁸

Hyperthyroidism (Grave’s disease)

Symptoms of an overactive thyroid include weight loss with increased appetite, tremor, racing heart, increased sweating, soft nails and hair, diarrhoea, palpitations, restlessness, irritability and raised blood pressure. Also with Grave’s disease there can be bulging of the eyes known as exophthalmos.

Herbs can be used to regulate an overactive thyroid, and there are two key plants, both members of the mint family, that have been used by herbalists for many generations to calm an overactive thyroid. They are Lycopus (bugleweed) and Leonurus (motherwort). The recent evidence suggests that they mainly counter the cardiovascular symptoms (see the bugleweed monograph).

In addition, the following therapeutic goals related to the autoimmune aspects could be considered:

Antithyroid dietary components should be encouraged (see previous).