Folate Deficiency: Awareness is key

An Overview Of Folate Deficiency And Problems With Insufficient Vitamin B12 Levels.

We take a lot for granted. I’m sure most of you reading this drive a car — and for most, like me, you hop in, turn the key, it starts, and off you go. On a daily basis, all the car requires to keep it moving is fuel, which you add periodically when needed.

However, whilst fuel is all that is required to keep the car moving, it’s the regular maintenance and monitoring of engine essentials like oil and a variety of other ‘bits’ that maintain the vehicle’s ability to keep the engine going once the fuel has been added.

The car is going nowhere if the engine is broken, whether the tank’s full or not! With regular preventative and protective maintenance, however, the engine will last for tens of thousands of miles. Conversely, failure to carry out routine maintenance and servicing will result in more catastrophic breakdowns and higher mechanics’ bills. In many ways, our bodies work in a similar way.

Yes, much like a car, it needs simple fuel such as carbohydrates, glucose, protein, etc, to keep us going through the day. However, like the car engine, to maintain body and mind longevity that will keep us fit and healthy for a lifetime, we need the essential nutrients provided by vitamins to maintain and protect our bodies’ vital systems and functions, ensuring that we too are good for a couple of hundred thousand miles.

To conclude the car analogy, ultimately, for most, the car will be replaced periodically with a newer, shinier model — whilst we only have the one body to last us our lifetime. It is vital therefore that we maintain a preventative and protective regimen to avoid breakdown, as Home Start and Roadside Recovery are not tick-the-box options. For the purposes of this article, we will look at the role of B vitamins, in particular B9 and B12 and their role in maintaining vital body and mind function, and what can be done if they’re not naturally available in the quantities we need.

B VITAMINS — USEFUL EVERYWHERE

There are eight B vitamins (B-complex vitamins), which together form the essential building blocks of a healthy body and mind. In general terms, they help the body to convert the food we consume into the fuel we need to function normally.

For most of us, if we are maintaining a healthy and balanced diet, we will get all the B vitamins our body needs through our food. In normal function, the body will take what it needs and as B vitamins are water-soluble, the body does not store them, with any excess being excreted through urine.

If the body’s ability to absorb vitamins is impaired for any reason, this is when deficiency may occur and remedial action through a supplement may be required. Vitamin B12 (cobalamin) is vital to the production of red bloods and DNA, as well as maintaining healthy nerve function.

Vitamin B9 is an essential nutrient that occurs naturally as folate (from the Latin folium, meaning leaf, which gives a great lead to a good source of B9 — leafy green vegetables). B9 works with B12 in the production of red blood cells and is also essential to healthy DNA formation. Folic acid is a synthetic version of folate, which can be taken as a supplement for a variety of uses:

• In deficiency cases — used as a supplement to increase folate levels.
• In pregnancy, for both pre-conception and during pregnancy to aid foetal brain, spine and skull development and help minimise risk of development problems.
• Can be used to alleviate side-effects of certain medicines, particularly methotrexate.
• When taken as a supplement, can help reduce high levels of homocysteine — an amino acid which can be an indicator for cardiovascular disease.

AN IRISH PERSPECTIVE

In a study conducted by The Irish Longitudinal Study on Ageing (TILDA) at Trinity College Dublin and published in the prestigious British Journal of Nutrition in 2018 (part of the largest representative study of its kind, with some 8,500 Irish older persons taking part in the initial response phase), results identified for the first time that a significant number of Irish adults +50 years old were at risk of deficiency in vitamin B12 and folate (linked to vitamin B9 folic acid).

As both B12 and folate are vital in maintaining primarily brain health, nerve function and the production red blood cells, along with many other functions, studies show that any deficiency in these essential nutrients can be directly linked to poor long-term health in this older age group.

Whilst the ultimate focus of the study was to mitigate for the fortification of foods (more discussion later), some of the key findings for the studied group were:

• For adults over 50:
• 12.5 per cent (one-in-eight) indicated low-to-deficient in B12; and
• 14.3 per cent (one-in-seven) low-todeficient in B9 folate.
• Prevalence of deficiency increased with age (14 per cent for 50-to-60 years to 23 per cent for +80 years).
• Low folate status was more common in smokers, the obese and those living alone.
• For B12, common groups as above, with the addition of a lower socio-economic marker.
• Alarmingly, results also indicated that whilst the use of any supplement to redress the shortfall was higher among women, the overall figure using supplementation of any kind within the test group was less than 4 per cent. It would appear obvious therefore that anything that could be done to increase the use of supplements, especially at an earlier stage of life, would offer more of the ‘preventative’ benefits discussed earlier and have nothing but positive health benefits in the longer term.

B12 AND FOLATE DEFICIENCY

As mentioned earlier, in normal function, our body derives its vitamin requirements from our food. There are circumstances, however, where deficiency can occur and lead to complications. As B12 has a major role in the production of red blood cells, any shortage can cause the body to produce abnormally large red blood cells, resulting in impaired cell function. Being larger, there are then fewer blood cells, aka anaemia, specifically, folate deficiency anaemia.

CAUSES OF DEFICIENCY MAY INCLUDE:

Pernicious anaemia is the most common cause of B12 deficiency in Ireland. Vitamin B12 absorption is prevented due to the immune system attacking healthy cells in the stomach. It is more common in women than men and can have an inherited family factor also. Once identified, this is easily treated with regular supplement injections.

Diet-based deficiency. Vitamin B12 is found in meat, fish, eggs, and milk — not in fruit and veg — so there may be potential issues for those choosing a vegan diet or chasing ‘fad’ diets, or those whose diet is unbalanced and who are not using a B12 supplement to provide essential nutrients.

Drug-related issues — drugs used for other conditions may affect levels of absorption of vitamin B12. The most common example is metformin in treating diabetes. Other drugs include colchicine, neomycin, and some anticonvulsants used to treat epilepsy, ie, phenobarbital. As stomach acid triggers B12 release from food, the long-term use of drugs that affect stomach acid production, such as H2 blockers and PPIs, can increase B12 deficiency. Some of the symptoms and issues arising from B12 deficiency can include:

Low energy levels.

• Extreme fatigue.
• Paraesthesia (pins and needles).
• Tongue inflammation and /or mouth ulcers.
• Muscle weakness.
• Psychological issues.
• Cognitive function issues.

TREATMENT

Once identified, generally following a GP visit and examination of symptoms and blood tests to identify the nature and extent of B12 or folate deficiency, a course of treatment of either injections or tablets will be recommended to replace the shortfall in vitamins. Vit B12 injections (given by intramuscular injection): One of two types used to treat Vit B12 deficiency anaemia:

• Hydroxocobalamin (usually preferred, as it is active in the body for longer).
• Cyanocobalamin (less used nowadays, as hydroxocobalamin stays active in the body for longer). Dosage depends on the level of deficiency but is often initially given on alternate days for up to two weeks, depending on improvement. Progress from this stage will depend on the nature of the deficiency, ie, whether it’s related to diet or not. If diet-related, B12 tablets may be prescribed to take daily between meals. Alternatively, a further course of injections, twice-yearly, may be more suited. If the B12 deficiency is not diet-related, then the usual choice is hydroxocobalamin injections every two-to-three months.

FOLIC ACID

Folic acid is a synthetic version of vitamin B9 and is generally prescribed as a supplement where needed:

• Before and during pregnancy.
• To manage and improve folate deficiency.
• To supplement a lack of dietary folate.
• To supplement folate levels for certain health conditions.
• To help alleviate side-effects of other treatments.

With folate anaemia, a daily folic acid tablet will usually be prescribed in addition to a dietary review to ensure that folate intake can be increased sustainably. For most, tablets will need to be taken for up to four months, although if there is no marked improvement, it could be a daily life-long dose. As mentioned earlier, for most, folate intake can be achieved through diet.

Excellent sources of naturally-occurring folate include:

• Any leafy greens (spinach, kale, asparagus, broccoli).
• Pulses (peas, lentils, chickpeas, any sort of ‘bean’).
• Oranges and fresh unsweetened orange juice.
• Fresh fruit.
• Bran and wholegrain.
• Poultry.
• Shellfish (especially oysters).
• Beef and liver (not if pregnant, due to high vitamin A). As you can see from above, given the range of sources, a balanced folate-rich diet can be easily achieved.

A note on cooking — heat destroys folate, so food shouldn’t be overcooked, and vegetables steamed or microwaved.

Daily dietary recommendations for folic acid are as follows:

Children

• Infants: 0-to-6 months: 65mcg.
• Infants: 7-to-12 months: 80mcg.
• Children: 1-to-3: 150mcg.
• Children: 4-to-8: 200mcg.
• Children: 9-to-13: 300mcg .
• Teens: 14-to-18: 400mcg. Adults
• Men and women over 19: 400mcg.
• Pregnant women: 600mcg.
• Breastfeeding women: 500mcg.

Another source of folate is in fortified cereals and other foods. The earlier reports on deficiency in the over-50s was largely carried out to explore the mandatory fortifying of certain foods.

There is no EU policy on fortifying foods, however the UK and Ireland adopt a policy of ‘voluntary but liberal’, so there are foods on the market that are folate-fortified.

With such a low uptake of supplements in the over-50s (4 per cent) — weighed against the increasing numbers within the age bracket showing deficiency — there are recommendations to educate on the lasting benefits of fortified foods, most commonly grains and cereals, from a much earlier age.

There is some evidence from the US, where folate fortifying is mandatory, of a significant reduction in the incidence of neural tube defect-related conditions.

BEFORE AND DURING PREGNANCY

If planning to have a baby, then ideally 400mcg of folic acid should be taken daily from three months before pregnancy, continuing through the first trimester.

There is so much vital foetal development in the earliest days of pregnancy (even before the first period is missed) that can benefit from increased folic acid intake. The risk of the baby developing any neural tube defects such as spina bifida, anencephaly or encephalocele (types of birth defects) is halved through a daily intake of folic acid, and the earlier the better if pregnancy is ‘planned’. If there is a risk of anaemia, a daily dose might be advised throughout the term of the pregnancy.

As part of the initial session with the midwife, the risk of a neural tube defect will be assessed based on medical history of both the mother and fatherto- be, and recommendations as to folic acid dosage given, ie, if the mother has diabetes, it is likely that a daily 5mg dose would be prescribed. Post-pregnancy, there is some benefit in continuing the daily dose, especially if breastfeeding — there is no risk to the baby through breast milk, as the amount would be too small to have an adverse effect.

DEFICIENCY-RELATED CONDITIONS

Coeliac disease In a study by the renowned Mayo Clinic, results revealed that someone with coeliac disease and the nature of its action on the digestive system was 10 times more likely to be suffering from a folate deficiency. In this case of women of child-bearing age, this figure was particularly alarming, given the risks associated with low folate levels and neural tube defect risk and risk for foetal development.

It recommended that there should be a move towards education of the quality on the diet ‘all the time’, factoring-in folate-rich foods, rather than simply the traditional binary choice of ‘foods to eat and foods not to eat’. Crohn’s disease For those with Crohn’s disease, vitamin B12 deficiency is commonly experienced. Given that B12 is absorbed in the lower part of the small intestine (ileum) and that this is commonly surgically removed as part of Crohn’s treatment, the result is that B12 is not properly absorbed, which creates the deficiency.

It is likely that B12 would have to be taken in some supplement form to maintain sufficient levels of red blood cells. Folate deficiency is less common for Crohn’s. A folic acid supplement is generally prescribed when other drugs used to manage inflammatory bowel disease (IBD) are prescribed, such methotrexate or sulfasalazine.

DEFICIENCY RELATED TO MEDICATION

Methotrexate In its general action, methotrexate reduces the amount of folic acid in the body in those taking methotrexate for rheumatoid arthritis or psoriasis. Taking a folic acid supplement can help alleviate the effects of the drug. Folic acid reduces the toxicity of methotrexate without any adverse impact on its efficacy.

The most prescribed dosage is 5mg taken the day after the methotrexate dose. The folic acid dose should be maintained throughout the course of methotrexate treatment. For those taking methotrexate for cancer-related treatment, folic acid should be avoided, unless specifically ordered by their doctor.

Research has indicated that folic acid may interfere with the drug’s effect on the cancer.

OTHER CONTRAINDICATIONS

Tetracycline (an antibiotic used to treat a broad range of infections, especially in those allergic to penicillin): Folic acid should not be taken at the same time as tetracycline, as folic acid reduces the absorption and effectiveness of tetracycline. Therefore, if taking both, folic acid should be taken at different times from tetracycline.

Phenytoin is an anti-seizure medication that may lower levels of folate in the body, and folic acid may interfere with the way phenytoin works, raising the risk of seizures.

Pyrimethamine: Used to treat malaria and to treat toxoplasmosis (an infection caused by exposure to the toxoplasma gondii parasite, mainly due to undercooked contaminated meat or exposure to cat faeces). Folic acid reduces its efficacy.

MEDICATIONS THAT LOWER LEVELS OF FOLIC ACID:

The following medications may interfere with the body’s absorption of folate, meaning a folic acid supplement may be needed while taking them. The prescribing doctor should be consulted in all cases.

• Antacids.
• H2 blockers: Used to reduce stomach acid, including cimetidine, famotidine, and ranitidine.
• Proton pump inhibitors: Used to reduce stomach acid, including esomeprazole, lansoprazole, omeprazole, and rabeprazole.
• Bile acid sequestrants: Used to lower cholesterol, including colestipol, cholestyramine and colesevelam.
• Anti-seizure medications: Including phenobarbital, primidone, and carbamazepine.
• Nonsteroidal anti-inflammatory drugs (NSAIDs): Including ibuprofen and naproxen.
• Sulfasalazine: Used to treat inflammatory bowel disease (IBD) and rheumatoid arthritis (RA).
• Triamterene: A diuretic that is rarely used nowadays.
• Cycloserine: An antibiotic used for tuberculosis.
• Pyrimethamine: Used to prevent and treat malaria and to treat toxoplasmosis.
• Trimethoprim: An antibiotic used to treat urinary tract infections.
• References: Available upon request

Disclaimer: Brands mentioned in this article are meant as examples only and not meant as preference to other brands.

CONTRIBUTOR INFORMATION

Written and researched by Eamonn Brady (MPSI), owner of Whelehans Pharmacies in Mullingar Tel 04493 34591 (Pearse St) or 04493 10266 (Clonmore). www. whelehans.inet. Eamonn specialises in the supply of medicines and training needs of nursing homes throughout Ireland. Email ebrady@whelehans.ie