What are the benefits and risks of using Phosphatidylserine (PS) and Docosahexaenoic acid (DHA) supplements?

Benefits and Risks of Phosphatidylserine (PS) and Docosahexaenoic Acid (DHA) Supplements

There is insufficient evidence to recommend routine supplementation with PS and DHA for general health benefits, and these supplements should primarily be obtained from food sources rather than supplements for most individuals. 1

Overview of PS and DHA

DHA (Docosahexaenoic Acid)

• Long-chain omega-3 fatty acid naturally found in fatty fish (salmon, tuna, mackerel)
• Essential component of brain cell membranes
• Important for brain development and function throughout life

Phosphatidylserine (PS)

• Phospholipid component of cell membranes
• Concentrated in brain tissue
• Can be derived from soy or other sources in supplement form

Evidence-Based Benefits

Cardiovascular Benefits of DHA

• Multiple meta-analyses show DHA (with EPA) may reduce risk of cardiovascular events, particularly in high-risk populations 2
• Dose-dependent effects observed for myocardial infarction reduction (9% risk reduction per additional 1g/day) 2
• Most significant benefits seen with doses ≥900 mg/day of EPA+DHA 2
• Particularly beneficial for patients with hypertriglyceridemia (≥1.50 g/l) 2

Neurological Benefits

• DHA is essential for brain development in infants and maintenance of normal brain function in adults 3
• PS supplementation (200 mg/day) showed improvement in ADHD symptoms and short-term auditory memory in children in a small randomized trial 4
• Combination of DHA and PS may help maintain hippocampal PS levels and DHA concentration in aged mice 5

Cancer-Related Benefits

• Long-chain N-3 fatty acids may help stabilize appetite, body weight, and reduce symptoms of anorexia and fatigue in cancer patients undergoing chemotherapy 2
• Some studies showed improvements in physical activity and quality of life with fish oil supplementation during chemotherapy 2

Limitations and Risks

Limited Evidence for General Population

• The American Diabetes Association and American Heart Association do not recommend omega-3 supplements for general prevention, instead suggesting obtaining fatty acids from food sources 1
• Only at very high doses (4g/day of EPA) was there evidence of cardiovascular benefit, and only in specific populations 1

Safety Considerations

• When supplemented in usual doses, fish oil and long-chain N-3 fatty acids are generally well-tolerated 2
• Mild gastrointestinal effects may occur; fishy aftertaste or fish belching may impair compliance 2
• Long-term supplemental intakes of EPA and DHA combined up to about 5 g/day do not appear to increase bleeding risk 2
• Caution in patients receiving ibrutinib (used in chronic lymphocytic lymphoma treatment) due to potential increased risk of epistaxis 2

Inconsistent Research Results

• Several randomized trials with 60-518 participants showed no benefit of supplemental fish oil intake 2
• Systematic reviews from 2007-2012 concluded insufficient evidence for long-chain omega-3 fatty acids to treat cancer cachexia 2
• The STRENGTH trial showed no cardiovascular benefit of EPA+DHA carboxylic acids in high-risk patients with mixed dyslipidemia 2

Special Populations Who May Benefit

Cardiovascular Disease Patients

• Patients with established cardiovascular disease and hypertriglyceridemia may benefit from higher-dose omega-3 supplementation 2
• Most significant benefits seen in secondary prevention with about 20% decrease in CHD death and 30% decrease in CHD events with doses ≥900 mg/day 2

Cancer Patients

• Cancer patients undergoing chemotherapy may experience improvements in appetite, energy intake, and body weight with fish oil supplementation 2
• Beneficial effects particularly observed in trials studying patients undergoing chemotherapy 2

Menopausal Women

• Declining estrogen production during menopause has implications for body tissue LCn-3 PUFA status 2
• The role of EPA and DHA in dampening chronic low-grade inflammation may be especially important during menopause 2

Clinical Approach to Supplementation

1. Prioritize food sources first:

   • Recommend fatty fish consumption (salmon, tuna, mackerel) at least twice weekly
   • Focus on obtaining fatty acids through diet rather than supplements

2. Consider supplementation only for specific conditions:

   • Severe hypertriglyceridemia (3-4g/day of omega-3)
   • Cancer patients with cachexia or undergoing chemotherapy
   • Established cardiovascular disease with persistent hypertriglyceridemia

3. Dosing considerations:

   • For cardiovascular benefit: ≥900 mg/day of EPA+DHA
   • For cancer-related symptoms: 1.5-2 g/day of long-chain fatty acids
   • For PS supplementation in cognitive concerns: 200 mg/day (limited evidence)

4. Monitor for side effects:

   • Gastrointestinal symptoms
   • Potential drug interactions (especially with anticoagulants and ibrutinib)

In conclusion, while PS and DHA have demonstrated benefits in specific populations, routine supplementation for general health is not supported by current evidence. The focus should be on obtaining these nutrients through dietary sources, with supplementation reserved for specific medical conditions under healthcare provider guidance.