Fatigue:
what to test before you treat

Vitamin B12

Vitamin B12 deficiency is real but not common in the general population. In NHANES 1999 to 2004, about 1% of US adults over 19 had clear deficiency, meaning low serum B12 with raised methylmalonic acid (MMA). About 5% had raised MMA alone, which can be an early sign.

The test that matters is serum B12 with MMA, not B12 alone. The estimates depend on the cutoff: depending on the cutoff used, low B12 status ranged from 3% to 26% of adults when measured by serum B12 alone.

In people whose B12 is normal, a trial of 95 adults aged 18 to 65 with IBS or IBD and fatigue found no fatigue benefit from 1,000 µg a day for eight weeks compared with placebo. Injections matter when the level is low. They are not a general energy fix.

Thyroid

Thyroid tests are the usual first check when tiredness comes with cold intolerance, weight change or dry skin. In NHANES III, about 0.3% of US adults had overt hypothyroidism and about 4.3% had subclinical hypothyroidism, meaning a raised TSH with a normal free T4 (Hollowell 2002). Subclinical findings are common, and they often do not explain symptoms.

In a randomized, placebo-controlled trial of 737 adults aged 65 and older with persisting subclinical hypothyroidism, levothyroxine restored normal thyroid function but did not improve the two primary outcomes, the hypothyroid symptom score or the tiredness score, after one year (TRUST, 2017). Treating diagnosed hypothyroidism is a different question, and it is what our thyroid products are for.

Sleep apnea

Sleep apnea is a common and often missed cause of daytime tiredness. A global analysis estimated that 936 million adults aged 30 to 69 had mild to severe obstructive sleep apnea, and 425 million had moderate to severe disease (Benjafield 2019). That analysis was funded by a sleep-device company, and its estimates depend on how the older studies were scored, so treat the exact numbers as estimates.

The test is a sleep study. Loud snoring, witnessed pauses in breathing and waking unrefreshed are the reasons to order one.

Testosterone, and women’s hormones

Low testosterone can cause low energy in men, and the number depends heavily on the definition. In a Boston-area population sample of men aged 30 to 79, symptomatic androgen deficiency (low total and free testosterone plus symptoms) was found in 5.6%, rising to 18.4% at age 70 and older (Araujo 2007). That study was partly supported by a drug company.

A low testosterone result is read with symptoms and the rest of the labs, not acted on alone. For women, hormone levels change with the menstrual cycle and with menopause, and this article does not include a prevalence figure for hormone-related fatigue in women.

Depression

Depression is one of the most common causes of persistent tiredness, often with poor sleep and less interest in things. The World Health Organization estimates that about 280 million people had depression in 2019, around 5% of adults, and that it is more common in women than in men (WHO).

A low mood score is a reason to talk about treatment and to rule out other causes. It is not a reason to start an energy supplement.

Vitamin D and omega-3 are not general energy fixes

Vitamin D and omega-3 are common add-ons when people feel run down. In the VITAL trial, 25,871 adults were randomized to vitamin D3 at 2,000 IU a day or to 1 g of omega-3 a day, each against placebo. Neither reduced major cardiovascular events or invasive cancer over a median of about five years (Manson 2019).

Vitamin D is a test-first decision. It is for people whose level is low or who have a clinical reason to take it, not a general energy product.

What this does not say

• Prevalence figures come from national surveys and population samples, and they depend on the cutoff used. A low rate in a population does not mean a low chance for you.
• The tests named here are common first checks, not a full list. Iron deficiency, anemia, medicines, alcohol, infections, and heart and lung disease also cause tiredness. This article does not include a sourced prevalence figure for iron.
• Trial results are averages for specific medicines, doses and groups. They are not predictions for one person.
• A supplement or an injection does not replace a diagnosis. Treating a confirmed condition is a different decision from treating a feeling.

Sources

1. 1.Pfeiffer CM et al. Vitamin B-12 status in the US population, NHANES 1999 to 2004. Am J Clin Nutr. 2011. American Journal of Clinical Nutrition
2. 2.Surplus vitamin B12 use does not reduce fatigue in patients with irritable bowel syndrome or inflammatory bowel disease: a randomized double-blind placebo-controlled trial. 2016. ScienceDirect
3. 3.Hollowell JG et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994). J Clin Endocrinol Metab. 2002;87:489-499. Journal of Clinical Endocrinology and Metabolism
4. 4.Stott DJ et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med. 2017. New England Journal of Medicine
5. 5.Benjafield AV et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019. Lancet Respiratory Medicine
6. 6.Araujo AB et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007. Journal of Clinical Endocrinology and Metabolism
7. 7.Depressive disorder (depression): fact sheet. World Health Organization. World Health Organization
8. 8.Manson JE et al. Vitamin D supplements and prevention of cancer and cardiovascular disease (VITAL). N Engl J Med. 2019. New England Journal of Medicine