Black cohosh
CONTRAINDICATIONS AND PRECAUTIONS Caution is advised in hyperthyroidism, as
bacopa has been shown to significantly elevate thyroxine levels in vivo. The clinical significance of this finding is unknown.
Brahmi may cause gastrointestinal symptoms in people with coeliac disease, fat malabsorption syndrome, vitamins A, D, E or K deficiency, dyspepsia or pre-existing cholestasis due to the high saponins content of the herb (Mills & Bone 2005).
PATIENTS’ FAQs
What will this herb do for me?
Brahmi has a long history of use as a brain tonic. Results from scientific studies demonstrate that it will enhance aspects of learning, memory and cog- nitive function with long-term use and is also likely to reduce anxiety,
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When will it start to work?
Studies indicate that 5–12 weeks’ continual use is required for benefits on cognitive function to become apparent. Acute effects may also be possible, but there is less evidence to be certain.
Are there any safety issues?
Information from traditional sources suggests that brahmi is well tolerated at the usual therapeutic doses and the most common side effects relate to gastrointestinal disturbances which are mild and reversible, such as nausea, frequent bowel motions and abdominal cramping. Clinical studies have not confirmed drug interactions so cautions are theoretical.
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Calcium
BACKGROUND AND RELEVANT PHARMACOKINETICS
In the context of both biosphere and biology (plant and animal) calcium plays a leading role. Its abun- dance in the environment (e.g. limestone, marble, coral) is reflected, in part, in the human body, with calcium being the most abundant mineral in the body. Calcium homeostasis reflects a balancing act between requirements for proper function and the organism’s need to protect against excess cellular calcium levels and associated toxicity. This balance has ramifications not only for our own physiology, but also in terms of levels and bioavailability of dietary calcium.
Three hormones regulate calcium status in the body — calcitriol (active vitamin D), parathyroid hormone (PTH) and calcitonin. Calcitriol increases intestinal absorption of dietary calcium when blood levels are low. In addition, PTH signals the kidneys to reduce calcium loss, produce more calcitriol and also activate osteoclasts that release bone calcium. Calcitonin is secreted by the thyroid gland when calcium levels become too high and opposes the action of PTH, thereby returning calcium levels back to normal.
Calcium, found in the diet or supplements, exists in salt form, from which it must be released for absorption to occur. Adequate hydrochloric acid levels are required to solubilise the majority of these calcium ions, failing which calcium salts entering the higher pH environment of the small intestine are more likely to precipitate and be rendered insoluble (Wahlqvist 2002). Low or moderate calcium intakes (≤400 mg/day) are absorbed via active trans- port mechanisms that are influenced by vitamin D. When intake is high, active transport mechanisms become saturated, leading to greater passive absorp- tion. Although most absorption occurs in the small intestine, the large intestine may also be responsible for up to 4% of absorption and provides compensatory mechanisms for those individuals
with compromised small intestine absorption (Groff & Gropper 2009).
Calcium’s bioavailability from both food and supplements shows substantial variation, and may be influenced by other foods present in the gastroin- testinal tract. Phytates (in wholegrains, nuts and seeds), oxalates, all types of fibres, unabsorbed dietary fatty acids and other divalent minerals all potentially compromise its absorption, while lactose (especially in children) and other sugars, as well as protein and the presence of vitamin D, all enhance uptake (Groff & Gropper 2009).
Calcium salts differ in the amount of elemental calcium, which may have clinical implications and affect dose selection. Calcium carbonate contains the highest amount of elemental calcium by weight (40%), calcium citrate (21%), calcium lactate (14%) and calcium gluconate (9%) (Kopic & Geibel 2013). In addition to having variable calcium fractions, the different calcium salts have widely divergent water solubility, which may also affect absorption and bio- availability. For example, calcium citrate dissolves 17 times more readily than calcium carbonate in water. However, 86% of calcium carbonate will still dissolve in a slightly more acidic environment (pH 5.5), which is higher than a normal maximum stomach pH of 4.5. Researchers in this area have not reached consensus as to whether the difference in water solubility is clinically relevant, provided the stomach pH is sufficiently acidic to dissolve the calcium supplement and allow for absorption (Kopic & Geibel 2013).
Besides the variation in absorption due to gastric pH, other dietary components and type of calcium salt, there are differences between individuals in their calcium absorption efficiency which can be up to 60% variance; the underlying mechanisms, although unclear, may be linked to vitamin D receptor (VDR) polymorphisms (Heaney & Weaver 2003). Consistent with this, our understanding of the magnitude of vitamin D’s influence upon
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suboptimal calcium has been linked to an increased risk of a range of other morbidities, including pre- eclampsia and colorectal cancer.
Deficiency signs and symptoms include: • tetany: muscle pain, spasms and paraesthesias • rickets
• osteomalacia
• increased neuromuscular irritability • altered heart rate
• ambulatory developmental delays in children • osteoporosis and increased risk of fractures • bone pain and deformity
• tooth discolouration and increased decay • hypertension
• increased risk of preeclampsia
• increased risk of colon cancer (controversial). There are many situations and conditions in which the risk of hypocalcaemia may be increased.
Primary deficiency
Primary deficiency occurs as a result of inadequate dietary intake, with greatest risk seen in populations with increased calcium requirements e.g. children, adolescents, pregnant and lactating women, post- menopausal women (particularly those taking hormone replacement therapy [HRT] [Wahlqvist 2002]), people experiencing rapid weight loss or patients receiving total parenteral nutrition (TPN).
Secondary deficiency
Calcium absorption is impaired in achlorhydria (more common in the elderly), intestinal inflamma- tion and any malabsorptive disorder accompanied by steatorrhoea (Wilson et al 1991). Increased faecal calcium loss occurs with higher intakes of fibre and in fat malabsorption, while renal excretion has been shown in some studies to be increased in those patients ingesting a high protein diet (Kerstetter et al 1998).
Factors that compromise vitamin D status or activity will also affect calcium status), e.g. oral and inhaled corticosteroids (Beers & Berkow 2003,
Pattanaungkul et al 2000, Prince et al 1997, Rossi et al 2005).
Other conditions that can predispose to hypocal- caemia include hypoparathyroidism (a deficiency or absence of PTH), idiopathic hypoparathyroidism (an uncommon condition in which the parathyroid glands are absent or atrophied), pseudohypoparathy- roidism (characterised not by deficiency of PTH, but by target organ resistance to its action), magne- sium depletion, renal tubular disease, renal failure, acute pancreatitis, hypoproteinaemia, septic shock or the use of certain medicines such as anticonvul- sants (phenytoin, phenobarbitone) and rifampicin, and corticosteroids (Beers & Berkow 2003, Rossi et al 2005).
MAIN ACTIONS
Calcium is an essential mineral required for the proper functioning of numerous intracellular and calcium absorption continues to broaden, including
the life-stage-dependent bioavailability of this mineral. The age-associated decline in calcium absorption (children absorb ≈75% compared with ≤30% in adults) (Groff & Gropper 2009) has now been linked to vitamin D via reduced available cal- citriol and decreased intestinal VDR levels, produc- ing vitamin D resistance (Groff & Gropper 2009,
Pattanaungkul et al 2000). Similarly, the decreasing bioavailability associated with (peri)menopause and the increased absorption evident early in pregnancy (Prentice 2003) are attributed largely to vitamin D-mediated effects. Calcium absorption, however, is described as being generally inefficient, with a substantial amount of calcium remaining unabsorbed in the lumen (Heaney & Weaver 2003).
Distribution results in 99% of absorbed calcium being deposited in bones. The remainder of the absorbed calcium is present in teeth and the intra- cellular or extracellular fluids. Calcium is excreted in faeces, sweat and urine.
FOOD SOURCES
Good dietary sources of calcium include dairy prod- ucts, fortified soy products, fish with bones (espe- cially salmon and sardines), tofu, broccoli, collard greens, mustard greens, bok choy, clams and black strap molasses. Certain brands of soy milk, fruit juice, breakfast cereal and bread are also fortified with calcium, which provides an alternative for people who don’t eat dairy products. People with limited dairy intake may still need to consider sup- plementation to ensure they meet RDI levels.
DEFICIENCY SIGNS AND SYMPTOMS
Optimal calcium intake is essential during every stage of life and insufficient intake in childhood years can have ramifications later in life.
While there is little information available about the prevalence of deficiency across the general Australian population, a Melbourne study of 1045 women aged 20–92 years in 2000 revealed that approximately 76% of women consumed calcium at levels less than the recommended daily intake (RDI), and an additional 14% demonstrated a grossly inadequate intake of less than 300 mg/day (Pasco et al 2000). Dietary calcium intake has been found to be inadequate and below Estimated Average Requirement (EAR) in the majority of elderly Australian women (Meng et al 2010). These figures are similar to those obtained by larger studies in the United States (Groff & Gropper 2009). Calculating the prevalence of calcium deficiency is partly hampered by physiological preservation of ‘non-osseous’ calcium for critical roles in exchange for the ‘expendable’ reserves in bone and, therefore, the slow development of overt deficiency features. Consequently, calcium deficiency is insidious in its early stages and potentially irreversible in the latter, making preventive optimisation the only suc- cessful pathway in all patients perceived to be at an increased risk. In addition to this, long-term
women. Acute severe hypocalcaemic states are treated initially with intravenous infusion of calcium salts. In chronic cases, oral calcium supplements are often combined with vitamin D supplements to improve absorption and utilisation.
Rickets and osteomalacia
A deficiency of either calcium or vitamin D can produce these bone disorders. (See Vitamin D monograph for further information.)
Infants
The percentage and type of fats within an infant formula and their ability to bind calcium salts and increase excretion has been shown to influence the bone mineral content (BMC) of infants. One hundred 8-week-old infants given formulas consid- ered to be more similar to breastmilk and less likely to form calcium soaps in the gut showed increased BMC after only 1 month’s treatment compared with those infants on standard formula (Kennedy et al 1999).
Bone mineral density (BMD), osteoporosis prophylaxis and reducing fracture risk
Calcium supplements are prescribed widely to promote bone health, including the treatment and prevention of osteoporosis, a major cause of mor- bidity and mortality in older people (Hennekens & Barice 2011). RCTs assessing BMD generally show a beneficial effect of calcium treatment in both men and women (typically a 1%–2% absolute difference between the treatment and control groups over 2–3 years), which results in a sustained reduction in bone loss of 50%–60%. The effect appears to be greatest for people whose baseline dietary calcium intake is low (Sanders et al 2009).
Adequate calcium intake is particularly important to consider in at-risk populations because osteoporosis-related fractures can lead to early dis- ability and death. Ensuring adequate calcium intake alone is not sufficient and vitamin D status is also important as both contribute to bone density and associated protective effects. Sufficient trace minerals such as manganese, zinc and copper and weight- bearing exercise is also suggested and the use of anti-resorptive drugs together with mineral supple- mentation may be required in high risk groups or those with preexisting osteoporosis.
The lifetime risk of fracture is highest in white women, and decreases successively among Hispanic, Asian and African-American people. For white women, it occurs 20% for the spine, 15% for the wrist and 18% for the hip, with an exponential increase in risk beyond the age of 50 years. Within 12 months after a hip fracture, approximately 13% of people die, with most survivors losing their previous independence. Calcium supplementation, together with vitamin D, may reduce vertebral and non-vertebral fractures (Vestergaard et al 2011). This is supported by a 2010 meta-analysis of seven randomised studies of vitamin D or calcium and extracellular processes, including muscle contrac-
tion, nerve conduction, beating of the heart, hormone release, blood coagulation, energy produc- tion and maintenance of immune function. It also plays a role in intracellular signalling and is involved in the regulation of many enzymes.
Bone and teeth mineralisation
Calcium is found in bone where it is mainly complexed with other ions in the form of hydroxy- apatite crystals. Approximately 1% of calcium in bone can be freely exchanged into the extracel-